As methods for administering drugs, various methods such as oral administration, rectal administration, subcutaneous administration, intravenous administration and the like have been known, and among them, oral administration has been widely employed. However, in the case of oral administration, it has been had disadvantages that drugs readily undergo primary metabolism in liver after absorption and that unnecessarily high concentrations of drugs in blood are transiently observed after administration. Also, lots of side effects such as gastrointestinal hepatic disorder, emetic feeling, anorexia and the like have been reported in oral administration.
Therefore recently, methods by percutaneous administration have been noticed as those which can be anticipated to achieve drug absorption safely and persistently for the purpose of solving such disadvantages of oral administration. The development of percutaneously administering preparations has been already advanced, and the products have been launched in the market.
However, because skin which has a barrier function to prevent invasion of foreign substances into body exerts a stronger barrier function against acidic drugs having salt-form, permeability of drugs is low and sufficient efficacy can not be anticipated. Thus, various attempts have been studied to enhance percutaneous absorption.
For example, Japanese Patent Publication No. 47535/1995 carries out the proposal that percutaneous absorption is enhanced by making a drug be free-form by adding stronger acidic organic acid than acidic drugs. However, the problem in which stability of the drug is lowered and problems such as irritation of skin and reduction of physical property of bases and the like induced by the added organic acid exist due to making the drug be free-form.
Also, ingenuity has been conducted in which percutaneous absorption of drugs is enhanced by combining percutaneous absorption accelerators. For example, the technique in which an absorption accelerator is combined with fatty acid ester (Japanese Patent Laid-Open No. 102656/1990) such as a combination of the absorption accelerator with a lower alkyl amide, for example, ethyl alcohol, isopropyl alcohol, isopropyl palmitate and the like with dimethyl acetamide (U.S. Pat. No. 3,472,931) has been proposed. However, it is a current status that these conventional absorption accelerators and absorption accelerating composition are highly irritative to the skin and thus it is still difficult to say that they are sufficient in safety.